Abstract
In 2009, Wang and colleagues reported the isolation of a structurally unique non-alkaloidal diterpene, atropurpuran, from Aconitum hemsleyanum var. atropurpureum. The structure of atropurpuran features an unprecedented cage-like skeleton consisting of five six-membered rings. Intriguingly, B, C, D, and E ring constitute the tetracyclo[5.3.3.0^<4'9>.0^<4'12>]tridecane skeleton into which two bicyclo[2.2.2]octane are comprised. Despite of these biosynthetically and structurally intriguing properties of tetracyclo[5.3.3.0^<4'9>.0^<4'12>]tridecane skeleton, no synthetic effort has been reported so far. Herein, we report the first entry for the construction of tetracyclic skeleton and the pentacyclic carbon framework of atropurpuran via an intramolecular reverse electron-demand Diels-Alder (REDDA) reaction of masked o-benzoquinone (MOB). The preparation of REDDA precursor was started from o-eugenol 1. Tetralone 4 was successfully converted to ketone 7. Reduction of ketone 7 with DIBAL, silyl etherification, followed by oxidation with Phl(OAc)_2 afforded REDDA precursor 10d. The REDDA reaction of silyl ether 10d (180℃, 1h) afforded tetracyclic 11d in high yield almost as a single diastereomer. Next, we proceeded to the construction of pentacyclic skeleton toward the total synthesis of atropurpuran. Addition of allylmagnesium bromide to ketone 7, ring-closing metathesis gave tricyclic 15. Oxidation of tricyclic 15 with Phl(OAc)_2 and followed by REDDA reaction of resulting MOB was achieved to construct the pentacyclic 14. Finally, hydrogenation of 15 and subsequent dehydration (Tf_2O, pyridine) afforded 16 to complete the construction of the pentacyclic framework of atropurpuran.
